The temporal topography of the N-Methyl- N-nitrosourea induced photoreceptor degeneration in mouse retina.
The temporal topography of the N-Methyl- N-nitrosourea induced photoreceptor degeneration in mouse retina.
复制标题
N-甲基-N-亚硝基脲的时间形貌诱导小鼠视网膜感光细胞变性。
DOI：
10.1038/srep18612
复制
发表时间：
2015-12-21
影响因子：
4.6
通讯作者：
Fei Huang Y
中科院分区：
文献类型：
--
作者：
Tao Y;Chen T;Fang W;Peng G;Wang L;Qin L;Liu B;Fei Huang Y
色素性视网膜炎（RP）是一组以进行性光感受器凋亡为特征的遗传性神经退行性疾病。n -甲基-n -亚硝基脲（MNU）是一种烷基化毒性物质，可引起与遗传性RP类似的光受体凋亡。然而，这种变性的详细过程模式仍然缺乏特征。我们系统地探索了MNU处理小鼠的光感受器变性的地形，并将这些空间数据与视网膜病理的时间依赖性特征联系起来。这些时间地形数据描绘了MNU处理视网膜中进行性光感受器变性的顺序场景：焦点光感受器对MNU毒性表现出不同的脆弱性，并表现出独特的空间和时间依赖性进展。此外，视网膜象限之间的位置不对称首次为MNU独特的毒理学特性提供了指导信息。进一步的机制研究表明，在MNU诱导的光感受器变性中，Bax和Calpain-2的上调而不是Caspase-3的上调可能是不对称的原因。结合两种光感受器群体对MNU神经毒性的比较敏感性，这些地形数据将有助于MNU诱导RP模型相关分析参数的标准化，并增强其在人类RP治疗探索中的应用。
Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases characterized by the progressive photoreceptors apoptosis. The N-Methyl- N-nitrosourea (MNU) is an alkylating toxicant which could induce photoreceptor apoptosis resembling that of the hereditary RP. However, the detailed process pattern of this degeneration remains poorly characterized. We systemically explored the topography of the photoreceptor degeneration in the MNU treated mouse, and related these spatial data with the time-dependent characteristics of retinal pathology. These temporal topographic data delineated sequential scenes of the progressive photoreceptor degeneration in the MNU treated retinas: focal photoreceptors showed different vulnerabilities to the MNU toxicity and displayed a distinctive spatial- and time-dependent progression. Moreover, the positional asymmetry between the retinal quadrants firstly provided instructive information about the unique toxicology properties of the MNU. Further mechanism study suggested that the up-regulation of Bax and Calpain-2, rather than the Caspase-3, should be responsible for the asymmetry in the MNU induced photoreceptor degeneration. Together with the comparative sensitivities to the neurotoxicity of MNU between two photoreceptor populations, these topographic data would facilitate the standardization of analytic parameters related to the MNU induced RP model, and enhance its application in the therapeutic explorations of human RP.